CPTH2 hydrochloride is a potent histone acetyltransferase (HAT) inhibitor. CPTH2 hydrochloride selectively inhibits the acetylation of histone H3 by Gcn5. CPTH2 hydrochloride induces apoptosis and decreases the invasiveness of a clear cell renal carcinoma (ccRCC) cell line through the inhibition of acetyltransferase p300 (KAT3B).

CTB is a p300 activator and the lowest docked energy for CTB and p300 is 7.72 kcal/mol.

CPI-1328 is an EZH2 inhibitor with a Ki value of 63 fM.

PRMT5-IN-15 is a PRMT5 inhibitor with an IC50 value of 0.84 nM.

EZH2-IN-6 is an EZH2 inhibitor with enhanced antitumor activity.

ODM-207 is a potent and selective BET inhibitor that is structurally unrelated to the benzodiazepine. ODM-207 also shows potent antiproliferative effects in patient-derived cancer cells and in xenograft models.

Phenylbutyrate is a potent histone deacetylases (HDACs) inhibitor. Phenylbutyrate can be used for urea cycle disorder research.

Cas9-IN-3 is a potent Cas9 inhibitor (IC50=28 μM). CRISPR/Cas systems have revolutionized gene editing in various species.

XP5 is a potent, orally active HDAC6 inhibitor with an IC50 of 31 nM. XP5 displays high antiproliferative activity against various cancer cell lines including the HDACi-resistant YCC3/7 gastric cancer cells (IC50=0.16-2.31 μM). XP5 enhances antitumor immunity when combined with a PD-L1 inhibitor in melanoma.

HDAC6-IN-3 (Compound 14), an antiprostate cancer agent, is a potent, orally active HDAC6 inhibitor with IC50s ranging from 0.02-1.54 μM for HDAC1/2/3/6/8/10. HDAC6-IN-3 is also an effective MAO-A (IC50=0.79 μM) and LSD1 inhibitor.

HDAC-IN-32 is a potent HDAC inhibitor with IC50s of 5.2, 11, and 28 nM for HDAC1, HDAC2 and HDAC6, respectively. HDAC-IN-32 possesses potent antiproliferation activities against tumor cells. HDAC-IN-32 shows potent antitumor efficacy in vivo That trigger antitumor immunity.

SIRT1 activator 3 is a potent activator of Sirt1 and suppresses TNF-α in a dose-dependent manner. SIRT1 activator 3 has the potential for anti-obesity or anti-diabetic researches.

BRD4-BD1/2-IN-1 is a potent BRD4 inhibitor with IC50s of <100 nM for BRD4 BD-1 and BRD4 BD-2, respectively (US20150148375A1, compound 5).

LW479, a novel HDAC inhibitor, could be a candidate drug for breast cancer prevention.

HDAC-IN-33 is a potent HDAC inhibitor with IC50s of 24, 46, and 47 nM for HDAC1, HDAC2 and HDAC6, respectively. HDAC-IN-33 possesses potent antiproliferation activities against tumor cells. HDAC-IN-33 shows potent antitumor efficacy in vivo That trigger antitumor immunity.

YF479, a novel HDAC inhibitor, displays more potent anti-tumor activity in vitro and in vivo compared with hydroxamic acid (SAHA).

Y08175 is a potent CBP bromodomain inhibitor. Y08175 exhibits considerable inhibitory effect with IC50s of 37 and 178.15 nM against CBP bromodomain in AlphaScreen assay and HTRF assay, respectively. Y08175 can be used for the research of prostate cancer.

HDAC-IN-28, a novel HDAC inhibitor, shows potent activities against tumor growth and metastasis

ZL0590 is a potent, orally active BRD4 BD1-selective inhibitor with an IC50 of 90 nM for human BRD4 BD1. ZL0590 exhibits significant anti-inflammatory activities.

WW437 is a histone deacetylase (HDAC) inhibitor with potent anti-breast cancer ability in vitro and in vivo.

Y08284 is a potent, selective, oral active CBP bromodomain inhibitor with an IC50 of 4.21 nM. Y08284 suppresses the proliferation of prostate cancer cell lines LNCaP, C4-2B, and 22Rv1. Antitumor activity.

1-Alaninechlamydocin, a cyclic tetrapeptide, is a potent HDAC inhibitor (IC50=6.4 nM). 1-Alaninechlamydocin induces G2/M cell cycle arrest and apoptosis in MIA PaCa-2 cells.

BRD4-BD1/2-IN-2 is a potent BRD4 BD2 inhibitor with IC50s of <0.5 nM and <300 nM for BRD4 BD2 and BRD4 BD1, respectively (WO2021233371A1, compound 2).

BRD4 D1-IN-1 is a selective BRD4 D1 inhibitor (IC50<0.092 µM). BRD4 D1-IN-1 has 18 nM affinity against BRD4 D1 and over 500-fold selectivity against BRD2 D1 and BRD4 D2 via ITC.

BRD4 D1-IN-2 (compound 26) is a potent and selective BRD4 D1 inhibitor (IC50<0.092 µM). BRD4 D1-IN-2 has 15 nM affinity against BRD4 D1 and over 500-fold selectivity against BRD2 D1 and BRD4 D2 via ITC.

Biotinylated-JQ1 (Biotin-JQ1) is a biotinylated derivative of JQ1 with high affinity for BRD4.

UNC6212 (Kme2), a dimethyllysine (Kme2)-containing ligand, has a KD for CBX5 of 5.7 μM.

UNC6349 (Ket2), a diethyllysine (Ket2)-containing ligand, binds to wild-type CBX5, with a KD of 3.2 μM.

Bomedemstat (IMG-7289) ditosylate is an oral and irreversible inhibitor of the epigenetically active lysine-specific demethylase 1 (LSD1) in mouse models of myeloproliferative neoplasms (MPNs). Bomedemstat can be used for the research of acute myelogenous leukemia (AML) and myelofibrosis (MF). Antineoplastic activity.

UNC6864 (Kei), an ethylisopropyllysine (Kei)-containing ligand, binds to wild-type CBX5, with a KD of 3.3 μM.

OARV-771 is a VHL-based BET degrader (PROTAC) with improved cell permeability. OARV-771 shows DC50s of 6, 1, and 4 nM for Brd4, Brd2 and Brd3, respectively.

Cas9-IN-2 is a potent Cas9 inhibitor (IC50=246 μM), Cas9-IN-2 acts by binding to apo-Cas9 to prevent Cas9:gRNA complex formation, which can potentially be applied to modulate and control Cas9 activity in various applications.

Cas9-IN-1 is a potent Cas9 inhibitor (IC50=7.02 μM), acting by binding to apo-Cas9 to prevent Cas9:gRNA complex formation.

OKI-006 is a potent and orally active inhibitor of histone deacetylase (HDAC). OKI-006 is a unique congener of the natural product HDAC inhibitor largazole. Histone deacetylases (HDACs) play critical roles in epigenomic regulation, and histone acetylation is dysregulated in many human cancers. OKI-006 has the potential for the research of cancer disease.

Elevenostat (JB3-22) is a selective HDAC11 inhibitor (IC50=0.235 µM). Anti-multiple myeloma (MM) activity.

MPT0B390 is an arylsulfonamide-based derivative with potent HDAC inhibitory ability. MPT0B390, TIMP3 inducer, inhibits tumor growth, metastasis and angiogenesis. MPT0B390 shows antiproliferative activity against human colon cancer cell line HCT116 with the GI50 of 0.03 μM.

MIR002 is a potent and orally active DNA polymerase α (POLA1) and HDAC 11 dual inhibitor. MIR002 induces acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. MIR002 shows significant antitumor activity in vivo.

PHD2/HDACs-IN-1 is a potent PHD2/HDACs hybrid inhibitor (IC50s of 1.15 μM, 19.75 μM, 26.60 μM and 15.98 μM for PHD2, HDAC1, HDAC2 and HDAC6, respectively). PHD2/HDACs-IN-1 is a low-toxicity renoprotective agent for research of cisplatin-induced acute kidney injury (AKI).

Snail/HDAC-IN-1 is a potent Snail/HDAC dual target inhibitor. Snail/HDAC-IN-1 displays potent inhibitory activity against HDAC1 with an IC50 of 0.405 μM and potent inhibition against Snail with a Kd of 0.18 μM. Snail/HDAC-IN-1 increases histone H4 acetylation in HCT-116 cells and decreases the expression of Snail protein to induce cell apoptosis.

HDAC-IN-30 is a novel multi-target HDAC inhibitor, including HDAC1 (IC50=13.4 nM),HDAC2 (IC50=28.0 nM), HDAC3 (IC50=9.18 nM), HDAC6 (IC50=42.7 nM), HDAC8 (IC50=131 nM). HDAC-IN-30 exhibits potent antitumor efficacy.

KD 5170 is a pan inhibitor of histone deacetylases (HDACs) and exhibits broad spectrum antitumor activity in vitro and in vivo.

MC4343 is a potent and dual inhibitor of EZH2 and histone deacetylase. MC4343 has the potential for the research of cancer disease.

NSC636819 is a competitive and selective inhibitor of KDM4A/KDM4B. KDM4A/KDM4B are potential progression factors for prostate cancer. NSC636819 has the potential for the research of cancer diseases, especially prostate cancer.

LSD1-IN-14 is a potent and selective LSD1 inhibitor (IC50=0.89 μM). LSD1-IN-14 can significantly inhibit the proliferation of A549 and THP-1 cells and induce the apoptosis of tumor cells.

AGK7 is a potent inhibitor of sirtuin 2 (SIRT2). AGK7 rescues alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. AGK7 protects against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease.

Sirt2-IN-5 is a potent SIRT2 inhibtor.

BRM/BRG1 ATP Inhibitor-2 is a BRG1/BRM ATPase inhibitor for the treatment of BAF-related disorders.

FHT-1205 is a potent SMARCA4/SMARCA2 ATPase (BRG1 and BRM) inhibitor with IC50s of ≤10 nM (WO2020160180A1; compound 67).

FHT-1204 is a potent SMARCA4/SMARCA2 ATPase (BRG1 and BRM) inhibitor with IC50s of ≤10 nM (WO2020160180A1; compound 70).

(R,R)-CFT8634 is a selective and orally active BRD9 protein degrader. (R,R)-CFT8634 has the potential for the research of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation (extracted from patent WO2021178920A1, compound 175).

(R,S)-CFT8634 is a selective and orally active BRD9 protein degrader. (R,S)-CFT8634 has the potential for the research of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation (extracted from patent WO2021178920A1, compound 176).

PARP1/BRD4-IN-1 is a potent and high selective PARP1/BRD4 inhibitor (IC50s of 49 and 202 nM in PARP1 and BRD4, respectively). PARP1/BRD4-IN-1 represses the expression and activity of PARP1 and BRD4 to synergistically inhibit the malignant growth of pancreatic cancer cells.

BRD4 Inhibitor-17 (Compound 5i) is a potent inhibitor of BRD4 with an IC50 of 0.33 μM. BRD4 Inhibitor-17 plays crucial role in regulating transcription of inflammatory, proliferation and cell cycle genes. BRD4 Inhibitor-17 serves as potential antidotes for arsenicals.

BRD4 Inhibitor-16 (Compound 4) is a potent inhibitor of bromodomain 4 (BRD4). Overexpression of bromodomain 4 (BRD4) is closely correlated with a variety of human cancers by regulating the histone post-translational modifications. BRD4 Inhibitor-16 represents a useful tool for explorative studies of BRD4 inhibition, such as an improved understanding of BRD4 inhibitor release-related information.

CREB-IN-1 TFA is a potent, orally active CREB inhibitor (IC50=0.18 µM). CREB-IN-1 TFA inhibits breast cancer cell growth.

TFMB-(S)-2-HG is a potent inhibitor of the 5'-methylcytosine hydroxylase TET2. TFMB-(S)-2-HG also inhibits the EglN prolyl hydroxylases. TFMB-(S)-2-HG has the potential for the research of acute myeloid leukemia (AML).

(S)-HH2853 (compound 200), a PYRIDINO five membered aromatic ring compound, is a potent EZH1/2 dual inhibitor with an IC50 of <100 nM for EZH2_Y641F. (S)-HH2853 has the potential to be used in the research of anti-tumor or autoimmune diseases.

(R)-HH2853 is a mutant EZH2 inhibitor with an IC50 of <100 nM for EZH2-Y641F. (R)-HH2853 can be used for cancer and autoimmune diseases (WO2018045971A1; compound 201).

MC4355 is a dual inhibitor of EZH2 and histone deacetylase (HDAC).

ORY-1001 (RG-6016) is a highly potent, selective inhibitor of lysine-specific demethylase KDM1A (LSD1) with IC50 of 18 nM, displays high selectivity for KDM1A over other FAD-containing monoamine oxidases.

NSD1 inhibitor BT5 is a covalent, small molecule inhibitor of NSD1 histone methyltransferase with IC50 of 1.4 uM, shows no covalent binding to NSD2.

KT-531 (KT531) is a potent, selective HDAC6 inhibitor with IC50 of 8.5 nM, displays 39-fold selectivity.

A potent and selective TAF1(2) bromodomain inhibitor.

AH237 (AH-237) is a potent and selective inhibitor for PRMT4 and PRMT5 with IC50 of 2.8 and 0.42 nM, respectively.AH237 (AH-237) displayed over 50-fold selectivity against a panel of 41 MTases such as PRMTs, PKMTs, NTMT1/2, and DNA methyltransferases (DNMTs), Its potency was also confirmed for PRMT1 (IC50 = 5.9 uM) and PRMT7 (IC50 = 831 nM).

ALKBH5 inhibitor 3 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 0.84 uM.

ALKBH5 inhibitor 6 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 1.79 uM.

ASH1L inhibitor AS-99 (AS-99) is a first-in-class, potent, selective inhibitor of ASH1L histone methyltransferase with IC50 of 0.79 uM.AS-99 strongly bind to the ASH1L SET domain with Kd values of 0.89 uM.AS-99 displayed no significant inhibition (>100-fold selectivity) at 50 uM against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2.AS-99 inhibits the growth of leukemia cells (MV4;11, MOLM13, and KOPN8) harboring different MLL1 translocations with the GI50 values of 1.8-3.6 uM, showed a several fold weaker effect on the proliferation of leukemia cells without MLL1 translocations, such as SET2 and K562, without toxicity in normal cells.AS-99 impairs transcriptional program of MLL fusion proteins and reduces leukemia burden.AS-99 reduced the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice.

BAY-155 (BAY155) is a novel, potent and selective menin-MLL inhibitor with binding IC50 of 8 nM, 10-fold better compared to that of MI-503; BAY-155 demonstrated a significantly enhanced selectivity profile compared to MI-503 in a panel of assays covering numerous safety pharmacology-relevant targets including GPCRs, ion channels and transporters. BAY-155 shows anti-proliferative activity in a large cell line panel, exhibits specific therapeutic activityin AML/ALL models.

BR-001 (BR001) is a potent, selective, allosteric inhibitor of EED subunit of PRC2 complex, disrupts EED-H3K27me3 interaction (IC50=4.5 nM).BR-001 directly binds to EED in the H3K27me3-binding pocket, BR-001 significantly increases the thermal stability of EED in thermal shift assay.BR-001 is selective for EED, has no activity against 371 wild-type kinases.BR-001 significantly reduced the cellular H3K27me3 level and also exhibited a strong antiproliferative effect in Karpas 422 cells.BR-001 inhibited proliferation of DLBCL cells and tumor growth, and upregulated target genes expression.BR-001 has potent antitumor efficacy in vivo, modulates immune response to suppress syngeneic CT26 colon tumor.

BRD4 D1 inhibitor 30 is a high-affinity, BRD4 D1-selective chemical probe with Kd of 18 nM, 500-fold selectivity against BRD2 D1 and BRD4 D2.BRD4 D1 inhibitor 30 down regulated inflammation, IL-8 and chemokine in cell based assays, but was unable to reduce c-Myc expression at low concentration in multiple myeloma cells.

BRD8 inhibitor DN02 is a first-in-class selective and cellularly active probe for NuA4 factor BRD8 (BD1) with IC50 of 34 nM, no affinity for BRD8 {BD2}, CBP, and p300.

BY27 (BD2 inhibitor BY27) is a potent, highly selective BET BD2 inhibitor with Ki of 8.9/8.2/14.2 nM for BRD2/3/4-BD2 respectively.BY27 displays 38-fold selectivity for BRD2-BD2 over BRD2-BD1.BY27 showed good antitumor activity in the MV4-11 xenograft model with an improved in vivo tolerance in mice compared with I-BET762.

CRCM5484 is a potent, BET BDII-selective inhibitor with IC50 of 130/20/71 nM for BRD4-BD2/BRD3-BD2/BRD2-BD2, respectively.CRCM5484 displays 475-fold selectivity over its first bromodomain (BRD3-BD2 vs BRD3-BD1).CRCM5484 demonstrates very low activity in various cell-based assays.CRCM5484 modulates the anti-leukemic activity in combination with various FDA-approved and/or in-development drugs in a cell- and context-dependent differential manner.

DC541 (DC 541) is a potent, selective peptidomimetic inhibitor of Protein N-terminal methyltransferase NTMT1 with IC50 of 0.34 uM; DC541 exhibits over 300-fold selectivity to several methyltransferases. DC541 inhibited funtions the cellular α-N-terminal methylation level of regulator of chromosome condensation 1 (RCC1, IC50 value of 30 μM) in human colorectal cancer HT29 cells.

DC-CBi-22 is a highly potent, selective CECR2 bromodomain inhibitor with IC50 of 8.0 nM, 24.9-fold selectivity over BPTF BRD.

DK1-04 is a potent, selective, cell-permeable small-molecule SIRT5 inhibitor with IC50 of 0.34 uM, shows no inhibition on SIRT1-3/6 at 83 uM.

DK1-04e (DK1-04 prodrug) is the prodrug of DK1-04, a potent, selective, and cell-permeable small-molecule SIRT5 inhibitor with IC50 of 0.34 uM; DK1-04e inhibits the cellular growth of breast cancer cells by targeting SIRT5. DK1-04e impairs mammary tumor growth in MMTV-PyMT transgenic mice and human breast cancer mouse model. SIRT5 inhibition suppressed the transformed properties of cultured breast cancer cells and significantly reduced mammary tumor growth in vivo, in both genetically engineered and xenotransplant mouse models.

ENL YEATS Domain inhibitor 7 is a selective, small molecule inhibitor of ENL YEATS Domain with IC50 of 0.62 uM in inhibiting the ENL-acetyl-H3 interaction.ENL YEATS Domain inhibitor 7 displayed strong selectivity toward the ENL YEATS domain over all other human YEATS domains.ENL YEATS Domain inhibitor 7 exhibited on-target inhibition of ENL in cultured cells and a synergistic effect with the bromodomain and extraterminal domain inhibitor JQ1 in killing leukemia cells.

FT108 (FT-108) is a potent, selective HDAC6 inhibitor (IC50=26 nM) relative to other HDAC family members (HDAC3 IC50=6.68 uM and HDAC8 IC50=4.07 uM).

FT234 (FT-234) is a selective HDAC11 inhibitor.FT234 demonstrated significant reduction in self-renewal stem-like SP cells with 2 uM FT234 or FT895, as well as the formation of vascular networks by SP cells at 5 uM compound treatment.FT234 significantly decreased the mRNA of Sox2 as well as its target genes like HK2 and PDK2 in SPAdh cells.FT234 compound inhibited the growth and viability by 60–80% in both A549 and H1650 cells at 5-10 uM, inhibited the viability of cancer cell lines A549 and H1650 ranged from 4.663–6.594 uM, reduced the viability of chemo-resistant cancer cells as well as chemo-insensitive CSCs.FT234 selectively prevent growth of cancer cells in presence of cancer associated fibroblasts (CAFs).

FTO inhibitor CS1 (NSC 337766) is a potent, selective small-molecule inhibitor of m6A demethylase FTO, inhibits m6A demethylation with IC50 of 142.6 nM in vitro (cell-free) assays.CS1 is highly efficacious FTO inhibitors with potent anti-leukemic efficacy againsta panel of leukemia cell lines with high FTO expression in vitro (IC50 range from 20 to 175 nM, MV4-11 IC50=58.9 nM).CS1 blocks the binding of FTO with its known target mRNAs, such as MYC, CEBPA, and RARA, notably increased global m6A abundance in AML cells, does not suppress the enzymatic activity of ALKBH5, or TET1.CS1 treatment resulted in substantially increased apoptosis and cell cycle arrest (at the G0 phase), also significantly promoted myeloid differentiation in human AML cells.FTO inhibitor CS1 substantially delayed AML progression and improved survival in AML PDX mouse model, significantly more effective than FB23-2.

GSK217 (GSK-217) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.5 (BRD4 BD2), 300-fold selectivity over BRD4 BD1.

GSK3543105 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 33 nM.

GSK3735967 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 40 nM.

GSK549 (GSK-549) is a potent, highly selective, BD2 domain-selective BET inhibitor with pIC50 of 7.8 (BRD4 BD2), 1150-fold selectivity over BD1.

GSK737 (GSK-737) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.3 (BRD4 BD2), 200-fold selectivity over BRD4 BD1.

HDAC3 inhibitor PT3 is a novel potent, selective, BBB-permeable HDAC3 inhibitor.PT3 exhibited higher selectivity for HDAC3 over HDAC1, HDAC6, and HDAC8 compared to the reference compound CI994.PT3 upregulated H3K9 acetylation, CREB 1, BDNF, TRKB, Nr4a2, c-fos, PKA, GAP 43 and MMP9 expression in mouse neuronal (N2A) cells.PT3 significantly improved the discrimination index in C57/BL6 mice in the novel object recognition (NOR) model, significant increased in H3K9 acetylation in hippocampus.PT3 upregulated CREB 1, BDNF, TRKB, Nr4a2, c-fos, PKA, GAP 43, PSD 95 and MMP9 expression in mice treated with PT3.

IMP-1575 (IMP1575) is a potent, selective Hedgehog acyltransferase (HHAT) inhibitor with Ki/IC50 of 38 nM/0.75 uM (Acyl-cLIP assay).IMP-1575 is the first sub-micromolar small-molecule HHAT inhibitor reported to-date.IMP‐1575 (50-0.023 μM) was therefore analyzed for effects on HHAT kinetics at varying Pal‐CoA concentrations (50–0.19 μM).IMP-1575 is a chemical tool and methodology to provide insight into HHAT which may expedite future studies and drug discovery efforts against this important target class.

iP300w is a potent p300/CBP inhibitor, inhibits p300-mediated H3K9 acetylation with IC50 of 33 nM in HTRF assay.iP300w diminishes DUX4-induced toxicity and inhibits DUX4-mediated transcription.iP300w blocks DUX4-induced H3 acetylation and prevents the increase in expression of DUX4 target genes, erases the DUX4-mediated transcriptional fingerprint in FSHD myoblasts.iP300w impairs DUX4-mediated transcription in vivo in the iDUX4pA FSHD mouse model.

IRBM6 (Class I HDAC-IN-6) is a potent, class I selective HDAC inhibitor with EC50 of 50 nM (HeLa cellular), HDAC1/2/3 IC50 of 1.7/2.8/1.1 nM.IRBM6 weakly inhibits HDAC6 (IC50=177 nM) and is inactive at 5 uM against HDACs 4-7.IRBM6 showed a potent inhibitory effect on the growth TC-797s and two additional NUT carcinoma (NC) cell lines, PER-403, and 10-15.IRBM6 induces a transcriptional program of differentiation in NC cells, demonstrated large-scale changes in gene expression that were significantly enriched with differentiation gene sets and depleted of pro-growth gene sets, including those of MYC and E2F targets.IRBM6 repressed growth and induced differentiation of NUT carcinoma (NC) cells in proportion to inhibition of NUT transcriptional activity.

KA2507 (KA-2507, KA 2507) is a potent and selective inhibitor of HDAC6 with IC50 of 2.5 nM, >300-fold selectivity over other HDACs.KA2507 demonstrated cellular potency (IC50=150 nM) in a cellular assay measuring induction of acetylated α-tubulin, a marker of HDAC6 inhibition.KA2507 displays antiproliferative effects against a set of 93 human cancer cells with IC50 of 2-30 uM.KA2507 inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model.

KDOBA67 is a novel cell-permeable inhibitor of H3K27 lysine demethylase KDM6A/B, inhibits TBXT expression chordoma cell lines.KDOBA67 displayed in vitro inhibitory activity in the low micromolar range with IC50 values of 2 to 5 uM in various chordoma cell lines, leading to induction of apoptosis.H3K27 demethylase inhibition via KDOBA67 alters chromatin state at TBXT and inhibits its expression.TBXT was a KDM6A/B target gene, and chromatin changes at TBXT following KDOBA67 treatment were associated with a reduction in TBXT protein levels.KDOBA67 treatment downregulated expression of a network of transcription factors critical for chordoma survival and upregulated pathways dominated by ATF4-driven stress and proapoptotic responses.

LM146 (LM-146) is a potent and selective inhibitor of pan-PB1 bromodomains (Polybromo-1 protein, PBRM1 or BAF180), binds to PB1(2), PB1(5), and SMARCA2B with KD values of 110, 61, and 2100 nM, respectively.LM146 displayed 34-fold selectivity profile for PB1(5) over SMARCA2, showed no binding to any bromodomains outside the sub-family VIII at 10 uM.PB1 (Polybromo-1 protein) is a component of the BRG1/BRM-associated factor (PBAF) complex, a human analog of the yeast switch/sucrose non-fermenting (SWI/SNF) complex. PB1 is a unique epigenetic reader that contains six distinct bromodomains, while other known bromodomain-containing proteins possess at most two bromodomains. The multi-subunit PBAF complex contains three bromodomain-containing proteins (BCPs): BRD7, a member of the sub-family IV, and SMARCA4 (also known as BRG1) and PB1, two members of the sub-family VIII.

LSH-A54 is a potent, class I selective HDAC inhibitor with IC50 of 26.2 nM (HDAC1) and 59.3 nM (HDAC2); LSH-A54 displays no significant inhibition against HADC3/6 (IC50>10 uM). LSH-A54 exhibits antiproliferative properties against breast cancer cell lines T-47D (IC50=1.58 uM), MCF-7 (IC50=1.32 uM) and BT-474 (IC50=2.55 uM). LSH-A54 attenuates cell migration significantly in wound healing assay and comparably to the pan-HDACi vorinostat, whereas the HDAC1-3 selective HDACi entinostat has no significant effect on cell migration. LSH-A54 reduced the number of colonies significantly in clonogenic survival assay compared to entinostat and showed comparable activity to pan-HDACi vorinostat.

MINA53 inhibitor 9 is a first in class, potent, selective MINA53 inhibitor with IC50 of 1.6 uM, selective over NO66, KDM4-6 and other JmjC oxygenases.

miR-21 inhibitor 12 (miR-21-IN-12) is a small molecule inhibitor of microRNA-21 expression and inhibit miR-21 transcription.miR-21-IN-12 inhibited transcription of the miR-21 gene resulting in significant reductions in primary and mature miR-21 levels.miR-21-IN-12 demonstrated cytotoxicity in a cervical cancer cell line via induction of apoptosis and was capable of reducing microtumor formation in a long-term clonogenic assay.miR-21-IN-12 shows some level of selectivity for miR-21 and is not a general miRNA pathway inhibitor.

MJM-1 is a small-molecule brain-penetrant HDAC inhibitor that increases the overall level of histone 3 (H3) acetylation in prostate cancer cell line.MJM-1 injected intraperitoneally (i.p.) crossed the BBB in mice and could be detected in the hippocampus, a brain region that mediates memory.MJM-1 (post-training i.p. administration) enhanced hippocampus-dependent spatial memory consolidation in male mice.

MO-I-500 is a pharmacological inhibitor of m6A demethylase FTO, inhibits purified FTO demethylase catalyzing demethylation with IC50 of 8.7 uM.MO-I-500 treated cells exhibited a global increase in RNA methylation.HeLa cells treated with 25 μM MO-I-500 for 24 hours showed a 9.3% increase in N6-methyl-adenosine content in total RNA.MO-I-500 treatment caused a dramatic (>95%) inhibition in colony formation in SUM149-Luc cells.MO-I-500 modulates various microRNA in treated (25uM) HeLa cells.MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells, with relatively little effect on cell growth.MO-I-500 can strongly reduce the adverse effects of streptozotocin (STZ) model of AD in human astrocytoma CCF-STTG1 cells.

MU1656 (MU 1656 ) is a potent, highly selective inhibitor of histone methyltransferase DOT1L with IC50 of 2 nM; MU1656 displays highly selectively against a panel of 37 methyltransferases. MU1656 is more metabolically stable and significantly less toxic in vivo than pinometostat.

MV1035 (MV-1035) is a novel small molecule that reduce U87 GBM cells migration and invasiveness, targeting m6A demethylase ALKBH5, also inhibits ALKBH2; MV1035 directly inhibits active recombinant ALKBH5 protein and, consequently, negatively regulates CD73 protein expression without affecting CD73 mRNA transcription. In PD-GSCs, MV1035 has a synergistic effect with TMZ in reducing cell viability and their ability to form spheres. MV1035 is able both to reduce the expression of MGMT and to inhibit ALKBH2 activity.

NAH-C3-GPKK is a potent, selective protein N-terminal methyltransferase 1 (NTMT1) bisubstrate inhibitor with Kiapp of 7 nM in endogenous proteomes.NAH-C3-GPKK also potently inhibit a methyltransferase complex HemK2-Trm112 (also known as KMT9-Trm112, IC50=0.3 uM).NAH-C3-GPKK is the first potent inhibitor for HemK2/KMT9.

NH4-13 is a potent, SIRT2-selective inhibitor with IC50 of 87 nM, no inhibition against SIRT1/3/5/6 (CI50>50 uM).NH4-13 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

NH4-6 is a potent, selective pan SIRT1-3 inhibitor with IC50 of 3.0/0.032/2.3 uM for SIRT1/2/3, respectively.NH4-6 does not inhibits SIRT5 and SIRT6.NH4-6 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

NN-390 (NN390) is a potent, selective HDAC6 inhibitor with IC50 of 9.8 nM, >200-550-fold selectivity over other HDAC isoforms.NN-390 inhibits primary cells of treatment-refractory Group 3 MB cells (SU_MB002) with IC50 of 2.33 uM.NN-390 is the first HDAC6-selective inhibitor to show therapeutic potential in metastatic Group 3 medulloblastoma (MB), an aggressive pediatric brain tumor often associated with leptomeningeal metastases and therapy resistance.NN-390 selectively targets cell population with a 44.3-fold therapeutic margin between patient-derived Group 3 MB cells in comparison to healthy neural stem cells.NN-390 demonstrated a 45-fold increased potency over HDAC6-selective clinical candidate citarinostat.

NR-160 (NR160) is a novel potent, selective inhibitor of histone deacetylase 6 (HDAC6) with IC50 of 30 nM, shows SI (75-1847 )over all HDAC class I isoforms.NR-160 induced α-tubulin acetylation (ac-α-tubulin) in treated acute myeloid leukemic (AML) cell line HL60, but not histone H3 (ac-H3) (a marker for the inhibition of class I HDACs).NR-160 enhances the cytotoxicity induction of bortezomib, epirubicin and daunorubicin on a panel of seven leukemia cell lines

NVS-BPTF-1 is the first highly potent and selective BPTF-bromodomain inhibitor with IC50 of 56 nM in an AlphaScreen assay and Kd of 71 nM in a BLI assay.NVS-BPTF-1 displays no significant interaction in DSF screen and a BROMOscan against a panel of other human bromodomains.In HEK293 cells, NVS-BPTF-1 showed on-target activity with an IC50 of 16 nM, as measured by a nanoBRET assay.NVS-BPTF-1 did not affect the proliferation of multiple human cancer cell lines, and NVS-BPTF-1 did not affect the level of PSMB8 and PSMB9 or TAP1 and TAP2, unlike BPTF siRNA knockdown caused effect.

OR-S0 is a potent, selective EZH2 inhibitor with IC50 of 11 nM, weakly inhibitor EZH1 (IC50=91 nM).OR-S0 inhibits H3K27me3 in HCT116 cells with IC50 of 24 nM, inhibited the growth of KARPAS‐422 cells in a dose‐dependent manner with GI50 of 210 nM.

ORY-1001 (RG-6016, Ladademstat) is a highly potent, selective inhibitor of lysine-specific demethylase KDM1A (LSD1) with IC50 of 18 nM, displays high selectivity for KDM1A over other FAD-containing monoamine oxidases; exhibits low nanomolar cellular activity (EC50 < 1 nM) in the THP1 differentiation assay and induces the CD11b marker within 6 hr of treatment in FACS based differentiation assay in THP1 cell line; induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML; exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of AML xenograft models.

PFI-5 a highly biochemically potent, selective, and cell-active SMYD2 chemical probe with IC50 of 8 nM.PFI-5 inhibits p53 methylation in MCF7 cells with EC50 of 1.3 uM, with no toxicity.

PRC2 EED-IN-1 is a potent, selective, allosteric, orally bioavailable inhibitor of the EED subunit of histone methyltransferase PRC2 with IC50 of 44 nM (H3K27me3 inhibition).PRC2 EED-IN-1 retains efficacy against EZH2 inhibitor-resistant cell lines (Karpas 44 cell IC50=27 nM), exhibits in vivo efficacy in EZH2-driven tumors in vivo.

PTG-0861 (JG-265) is a novel potent, selective HDAC6 inhibitor with IC50 of 5.92 nM, >36-fold selectivity over other HDACs.PTG-0861 (JG-265) displays HDAC6 cellular target engagement with EC50 of 0.59 uM (ELISA), has in vitro and cellular selectivity superior to HDAC6-selective inhibitor citarinostat (ACY-241).PTG-0861 (JG-265) demonstrates potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells and CD-1 mice.PTG-0861 (JG-265) exihibits promising in vitro pharmacokinetics achieved with good safety profile in cells and in vivo.

SGC3027N (SGC-3027N) is a negative control compound for SGC3027, shows markedly less potent (14 uM) against PRMT7 and other protein methyltransferases.

SGC6870 (SGC-6870 (R-isomer)) is a potent, selective, cell-active PRMT6 inhibitor with IC50 of 77 nM.SGC6870 displays outstanding selectivity for PRMT6 over a broad panel of other methyltransferases and nonepigenetic targets.SGC6870 binds to a unique, induced allosteric pocket of PRMT6.SGC6870 engages PRMT6 and potently inhibits its methyltransferase activity in cells.SGC6870 is a well-characterized PRMT6 chemical probe and a valuable tool for further investigating PRMT6 functions in health and disease.

SGC6870N is the negative control of SGC-6870 (R-isomer), which is a potent, selective, cell-active PRMT6 inhibitor.

SGC8158 (SGC-8158) is a potent, selective, and SAM-competitive inhibitor of PRMT7 with IC50 of <2.5 nM, the active component of it's cell permeable prodrug SGC3027.

SIRT2 inhibitor 55 is a potent and selective SIRT2 inhibitor with IC50 of 250 nM.SIRT2 inhibitor 55 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 55 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 55 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=11.9 uM).

SIRT2 inhibitor 56 is a potent selective SIRT2 inhibitor with IC50 of 780 nM.SIRT2 inhibitor 56 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 56 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 56 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=9.1 uM).SIRT2 inhibitor 56 induces apoptosis and shows anti-proliferation effect in OCI-Ly8-LAM53 (OCI) cells.

SIRT3 inhibitor 8 is a SIRT3 selective inhibitor with IC50 of 6 uM, 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2.SIRT3 inhibitor 8 reduced DLBCL cell viability and triggered activation of autophagy.

SIRT5 inhibitor 32 is an efficient, cellularly active small molecule that targets SIRT5.SIRT5 inhibitor 32 inhibits cell growth of SIRT5-dependent AML cell lines SKM-1, OCIAML2 and MOLM-13 with IC50 of 9, 20, and 24 uM, respectively.SIRT5 inhibitor 32 is also shown to inhibit SIRT5 in HeLa cells by using an assay that produce in-cell fluoresence in response to SIRT5 activity in the mitochondria.SIRT5 inhibitor 32 displays cytoselective toxicity towards SIRT5-dependent AML cells (SKM-1) over HEK293T cells in culture.

SIRT6 activator CL5D is a novel small-molecule activator of SIRT6 deacetylation, stimulates 4-fold activation of SIRT6 (1 uM) against H3K9ac (20 uM) at 3 uM.CL5D demonstrate competitive inhibition with Ki of 13.4 uM.CL5D exhibited time-dependent deacetylation at H3K9 by SIRT6 in HEK293T cells.

SJ018 (SJ-018) is a potent, highly selective BET BD2 inhibitor with Kd of 14 nM (BRD2-BD2), 67-fold selectivity over BRD2-BD1. SJ018 is more effective than JQ1 in increasing FRAP in cells, potently inhibits MV4-11 cell growth with GI50 of 2-3 nM (Days3-7).

SJ432 (SJ-432) is a potent, highly selective BET BD2 inhibitor with Kd of 6/2 nM (BRD2-BD2/BRD4-BD2), displays 80/152-fold selectivity over BD1, respectively.SJ432 is more water soluble than SJ018 (40 uM vs <0.1 uM).SJ432 potently inhibits MV4-11 cell growth with GI50 of 8 nM, is more effective than JQ1 at reducing levels of MYC protein in NB cell lines, upregulated p21& GADD45H and downregulated CCND2 & ODC1, C-MYC target genes.SJ432 (15 mg/kg, i.p.) significantluy reduced tumor volumes in pediatric NB xenograft SK-N-AS, with essentially no loss in body weight.

SKI-73 is a CARM1 chemical probe with pro-drug properties, can readily penetrate cell membranes and then be processed into two active CARM1 inhibitors.SKI-73 (10 uM) fully suppresses the methylation of BAF155 Arg1064 in MCF-7 cells.SKI-73 inhibits in vitro invasion but not proliferation of breast cancer cells ( MDA-MB-231 cell, EC50=1.3 uM).SKI-73 recapitulates the anti-invasion effect of the genetic perturbation of CARM1.Either CARM1 knockout or CARM1 inhibition with SKI-73 alters the epigenetic plasticity in a proliferation-independent manner by replacing the most invasion-prone subpopulation with the non-invasive subpopulation(s) to suppress the invasive phenotype.

SKLB-03176 (SKLB03176) is a potent, selective, covalent EZH2 inhibitor with IC50 of 47 nM, covalently binds to the SAM pocket of EZH2.SKLB-03176 showed good inhibitory activity against mutations EZH2 Y641F, EZH2 Y641N, and EZH2A677G at 200 nM concentration.SKLB-03176 exhibited weak activity against other targets, such as 5 histone methyltransferases and more than 30 kinases, >50-fold selective for EZH2 over the highly homologous H3K27 methyltransferase EZH1 (IC50=2.45 uM).SKLB-03176 inhibited the activity of a variety of EZH2 mutants and significantly inhibited the expression of H3K27Me3 in cells.SKLB-03176 showed no cytotoxicity to normal cells.

SMYD3 inhibitor 29 is a highly potent, selective, covalent inhibitor of histone methyltransferase SMYD3 with IC50 of 11.7 nM.SMYD3 inhibitor 29 exhibits high potency by inhibiting SMYD3's enzymatic activity and showing antiproliferative activity against HepG2 in 3D cell culture (GI50=1.04 uM).SMYD3 inhibitor 29 inhibits cellular MAP3K2 methylation.SMYD3 inhibitor 29 displayed high selectivity when tested against a panel of methyltransferases, namely, SMYD1-2, G9a, PRDM9, and PRMT5.

SRX3177 is a potent, triple BRD4/PI3K/CDK4/6 inhibitor with nanomolar potency against PI3Kα (IC50=79 nM), BRD4 bromodomains (BD1 and BD2) (IC50=33 nM and 89 nM, respectively), and CDK4/6 (IC50=2.5/3.3 nM).SRX3177 is capable of targeting BRD4, PI3K and CDK4/6 simultaneously, induces apoptosis and cell cycle arrest and has in vitro efficacy in mantle cell lymphoma, hepatocellular carcinoma and neuroblastoma models.SRX3177 has antitumor efficacy in in vivo xenograft models and is less toxic than the combination of agents that inhibit individual targets.

SRX3212 (SRX 3212) is a potent, dual BRD4/PI3Kα inhibitor with IC50 of 3.7 nM (BRD4 BD1) and 32 nM (BRD4 BD2), IC50 of 22 nM for PI3Kα.SRX3212 demonstrated strong anti-cancer activity in cyclinD1 dependent mantle cell lymphoma cell lines (Jeko-1, Mino and Z138), a colon carcinoma cell line (HCT116), a MYCN amplified p53 mutated neuroblastoma cell line (SKNBE2) and a PTEN mutated prostate cancer cell line (PC3), with nanomolar to low micromolar IC50 values.

SRX3262 is a potent, triple BTK/PI3K/BRD4 inhibitor.

SRX 3305 is a potent, triple BTK/PI3K/BRD4 inhibitor with IC50 of 6.5 nM, 15 nM, and 4 nM toward BTK, PI3Kɑ and PI3Kδ respectively, inhibits BRD4 BD1 and BD2 with IC50 of 77 and 95 nM.SRX3305 showed enhanced binding to the drug-resistant C481S mutant of BTK compared to SRX-3262 (IC50=9 uM and 25 uM, respectively).SRX3305 displayed cytotoxicity aginst MCL cell lines JeKo-1, Mino, Granta with IC50 of 58 nM, 1 nM, 1.1 uM, respectively.SRX3305 inhibited cell vbiability of JeKo-1 BTK C481S and Mino BTK C481S mutant cell lines with IC50 of 1 uM and 47 nM, respectively, with minimally toxic to healthy donor PBMCs.SRX3305 showed improved efficacy in MCL and Ibrutinib-resistant MCL cells, SRX3305 impacted gene expression, perturbs the cell cycle and promotes apoptosis in MCL.

SS-208 (SS208) is a novel potent, selective inhibitor of histone deacetylase 6 (HDAC6) with IC50 of 12 nM, >100-fold selectivity over HDAC1/4/5/7/8/9/11.SS-208 has minimal effects on the viability of murine SM1 melanoma cells in vitro, significantly reduced in vivo tumor growth in a murine SM1 syngeneic melanoma mouse model.

SW-101 (SW101) is a potent, selective HDAC6 inhibitor with IC50 of 0.7 nM, >200-fold selectivity over HDAC1/2/3.SW-101 possesses excellent HDAC6 potency and selectivity, together with markedly improved metabolic stability and druglike properties compared to SW-100.SW-101 treatment elevates the impaired level of acetylated α-tubulin in the distal sciatic nerve, counteracts progressive motor dysfunction, and ameliorates neuropathic symptoms in a CMT2A mouse model bearing mutant MFN2.

SW2_152F (SW2 152F) is a potent, selective, cell permeable CBX2 chromodomain probe, binds to the N-terminal chromodomain (ChD) with Kd of 80 nM.SW2_152F displays 24-1,000-fold selectivity for CBX2 ChD over other CBX paralogs (CBX4/6/7/8) in vitro.SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.

T-518 (T518) is a potent, highly selective, brain penetrant, oral HDAC6 inhibitor with IC50 of 36 nM.T-518 did not obviously inhibit human HDAC1, 4, or 7 at 10 uM, which belongs to Class I or Class IIa HDAC.T-518 showed brain penetration in an oral dose and blocked HDAC6-dependent tubulin deacetylation at Lys40 in mouse hippocampus.T-518 decreased RIPA-insoluble tau accumulation (3-month treatment, 1 and 3 mg/kg), restored impaired axonal transport and novel object recognition in the P301S tau Tg mouse (tauopathy model) by 2-week treatment with dose 1 and 3 mg/kg.

TACH101 (QC8222, TACH 101) is a reversible, α-ketoglutarate competitive, selective and potent inhibitor of KDM4 isoforms A-D with IC50 values of <0.1 uM against all four isoforms.TACH101 demonstrated potent increase of H3K36me3 levels (EC50 <0.001 uM, HTRF) in KYSE-150 cell line engineered to overexpress KDM4C and showed potent anti-proliferative activity in multiple cell lines in OncoPanel.Sub-micromolar levels of TACH101 induced apoptosis in human colorectal (HT-29), esophageal (KYSE-150), and triple negative breast cancer (MDA-MB-231) cell lines with EC50s of 0.033-0.092 uM.TACH101 triggered effective tumor growth control in xenograft models including colorectal, esophageal, gastric, breast, and lymphoma with tumor growth inhibition of up to 100%.

Targapremir-200c (TGP-200c) is a structure-specific, small molecule inhibitor of miR-200c precursor (pre-miR-200c), binds to the Dicer site of pre-miR-200c with Kd of 50 nM.TGP-200c inhibits Dicer processing of pre-miR-200c with IC50 320 nM, selectively engages pre-miR-200c in cells.TGP-200c potently inhibits miR-200c biogenesis selectively across the miRnome and modulates the downstream miR-200c pathway.TGP-200c selectively inhibits miR-200c over other miR-200 family members by recognizing the 1x1 UU internal loop unique to pre-miR-200c and an adjacent AU base pair simultaneously.TGP-200c selectively rescues a miR-200c-mediated phenotype in MIN6 cells, induces anti-apoptotic phenotype, modulates various T2D-related pathways, including insulin signaling and metabolism, represses pro-cell death factors and promotes β cell survival in specific ways.

TC-5115 (TC5115 ) is a potent, selective inhibitor of MLL1 SET domain with IC50 of 15 nM, 48 times more potent than the pan-methyltransferase inhibitor SAH.

TDI-11904 is a highly potent, and peripherally active EZH2 inhibitor.

TDI-6118 is a potent, selective brain-penetrant EZH2 inhibitor with IC50 of 14 nM, inhibits cellular H3K27me with IC50 of 580 nM.

TGP-377/421 (Targapre-miR-377/421) is a smalll molecule targets pre-miR-377 and inhibits its processing, binds to miR-377's Dicer processing site with Kd of 29 uM.TGP-377/421 inhibits the cellular biogenesis of miR-377 in HUVECs, reduced mature miR-377 levels in a dose-dependent fashion with IC50 of 5 uM, also inhibits miR-421.

Tucidinostat (Chidamide, HBI-8000, CS055) is a novel histone deacetylase (HDAC) inhibitor with IC50 of 95/160/67/733/78/432 nM for HDAC1/2/3/8/10/11, respectively; shows no activity against Class IIa HDAC4/4/7/9 and HDAC6; demonstrates significant and broad spectrum in vitro and in vivo antitumor activity, induces G1 arrest, ROS-dependent apoptosis and differentiation in human leukaemia cells.

UBD253 (SGC-UBD253) is a potent, selective ubiquitin chemical probe for ubiquitin binding domain of HDAC6 with Kd of 84 nM (SPR), inhibits the HDAC6-ISG15 interaction (EC50=1.9 uM, nanoBRET).UBD253 (SGC-UBD253) displays little to no affinity for other USPs (>100-fold selectivity). SGC-UBD253 potently (<100 nM) binds HDAC6-UBD (ubiquitin binding domain), decreases the interaction between full-length HDAC6 with ISG15.

UHRF1 PHD inhibitor MLD4 is a specific compound that selectively inhibits the UHRF1-histone interaction (IC50=12.4 uM), targets the PHD finger of UHRF1, specifically disrupting histone H3 arginine 2 interactions with the PHD finger.UHRF1 PHD inhibitor MLD4 inhibited binding between H3K9me3(FAM) and UHRF1 with IC50 of 24-26 uM, displace UHRF1-histone H3 binding in cells.

UHRF1 PHD inhibitor MLD5 is a specific compound that selectively inhibits the UHRF1-histone interaction (IC50=7.4 uM), targets the PHD finger of UHRF1, specifically disrupting histone H3 arginine 2 interactions with the PHD finger.UHRF1 PHD inhibitor MLD5 inhibited binding between H3K9me3(FAM) and UHRF1 with IC50 of 24-26 uM, displace UHRF1-histone H3 binding in cells.

UM-002 is a highly potent, selective, brain penetrant BRD4 bromodomain inhibitor with IC50 of 8.8 and 2.4 nM for BRD4-1 and BRD4-2, respectively.UM-002 is more potent than JQ1 at inhibiting BRD2-1, BRD4-1, and BRD4-2.UM-002 reduces GBM cell proliferation more than JQ1, or the brain penetrant BET inhibitor MK-8628.UM-002 not affect the enzymatic activity of histone deacetylases, histone acetyltransferases.UM-002 inhibits GBM cell proliferation in vitro with EC50 of 0.13 and 0.24 uM for GBM22 cells and GBM39 cells, repectively.UM-002 reduces proliferation of GBM cells co-cultured with cerebral brain organoids, reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors.

WDR5 inhibitor 41 is a potent, selective and orally bioavailable WDR5 WIN-site inhibitor with TR-FRET Ki value of <0.02 nM, inhibits cell proliferation of MV4:11 and MOLM-13 with IC50 of 13 and 27 nM, respectively.WDR5 inhibitor 41 is well tolerated in mice by both iv and po dosing and showed no clinical sign of abnormalities suggesting an enhanced safetyprofile for the series.

XP-524 (XL-223, XP524) is a potent, dual-BET/EP300 inhibitor, inhibits BRD4-BD (IC50=5.8 nM) and BRD4-BD2 (IC50=1.5 nM).XP-524 binds strongly to and inhibits EP300 and CBP proteins with IC50 of 28 and 116 nM, respectively.XP-524 (XL-223) showed high potency and selectivity (Kd < 1 nM) across BET family proteins. Selectivity for BRD proteins over all other bromodomain proteins was >400-fold.XP-524 significantly decreased expression of Myc pathway oncogenes such as c-MYC and n-MYC, increased expression of CDKN1B, a tumor suppressor that prevents the activation of the cyclin-D/CDK4 complex, and also reduced expression of cyclin-D (CCND1) itself.XP-524 showed increased potency and superior tumoricidal activity than the benchmark BET inhibitor JQ-1 in vitro, with comparable efficacy to higher-dose JQ-1 combined with the EP300/CBP inhibitor SGC-CBP30.XP-524 prevented KRAS-induced, neoplastic transformation in vivo and extended survival in two transgenic mouse models of aggressive PDAC.

XY153 is a potent, BD2-selective BET inhibitor with IC50 of 0.79 nM for BRD4 BD2, 354-fold selectivity over BRD4 BD1.XY153 displays 6-fold BRD4 BD2 domain selectivity over other BET BD2 domains.XY153 displayed potent antiproliferative activity against multiple tumor cell lines, especially MV4-11 (IC50=0.55 nM), also demonstrated good metabolic stability in vitro.

YC8-02 is a small molecule mitochondrial-targeting SIRT3 inhibitor with IC50 of 0.53 uM.YC8-02 inhibits SIRT1 and SIRT2 with IC50 of 2.8 and 0.062 uM in in vitro biochemical assays.YC8-02 manifested increased ratio of mitochondria to total cell concentration, as measured by mass spectrometry in purified mitochondria extracts and total cell lysates.YC8-02 increased mitochondrial protein acetylation, inhibited GDH activity and induced autophagy in DLBCL cells.YC8-02 could phenocopy the effects of SIRT3 depletion.YC8-02 (30 mg/kg) caused regression of the tumors in DLBCL xenografts, with no evidence of discomfort or weight loss.

[18F]-NT160, a Florbetapir (18F)-radiolabeled NT160, is a diagnostic tool for positron emission tomography (PET). NT160 is a brain-penetrant and selective class-IIa HDAC inhibitor with an IC50 of 46 nM. NT160 exhibits a remarkably high inhibition against HDAC4, HDAC5, HDAC7, and HDAC9 with IC50s of 0.08 nM, 1.2 nM, 1.0 nM, and 0.9 nM, respectively.

MI-1 inhibits Menin-MLL interaction with an IC50 of 1.9 μM.

2′,3′,5′-Triacetyl-5-azacytidine is an orally active prodrug of 5-Azacytidine. 5-Azacytidine is an inhibitor of DNA methyltransferase.

2-Hexyl-4-pentynoic acid ((±)-2-Hexyl-4-pentynoic acid), valproic acid (VPA) derivative, exhibits potential roles of HDAC inhibition (IC50=13 µM) and HSP70 induction. Potent neuroprotective effects. 2-Hexyl-4-pentynoic acid causes histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons.

Coumarin-SAHA is a fluorescent probe for determining the binding affinities (kd) and the dissociation off-rates (koff) of the HDAC8-inhibitor complexes.

JPS014 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS014 degrades class I histone deacetylase (HDAC). JPS014 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells.

JPS016 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS016 degrades class I histone deacetylase (HDAC). JPS016 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells.

JPS035 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS035 degrades class I histone deacetylase (HDAC). JPS035 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells.

JPS036 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS036 degrades class I histone deacetylase (HDAC). JPS036 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells.

MAK683 hydrochloride is an embryonic ectoderm development (EED) inhibitor extracted from patent US20160176882 A1, compound example 2. MAK683 exhibits IC50s of 59, 89, 26 nM in EED Alphascreen binding, LC-MS and ELISA assay.

RSC133 exhibits dual activity by inhibiting histone deacetylase and DNA methyltransferase. RSC133 effectively facilitates reprogramming of human somatic cells to pluripotent stem cells and supports the maintenance of an undifferentiated state of human pluripotent stem cells.

GEM144 is a potent and orally active DNA polymerase α (POLA1) and HDAC 11 dual inhibitor. GEM144 induces acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. GEM144 has significant antitumor activity in human orthotopic malignant pleural mesothelioma xenografts.

SDR-04 is a BET inhibitor and exhibits strong BRD4-BD1 affinity and inhibition activity. SDR-04 potently suppresses MV4;11 cancer cell line proliferation.

HC-Toxin, a cyclic tetrapeptide, is a potent HDAC inhibitor with an IC50 of 30 nM. HC-Toxin induces tumor cell apoptosis and has anticancer effects.

DS17701585 (Compound 11) is a highly selective, orally active EP300 and CBP inhibitor with IC50 values of 0.040, 0.15, 0.45 and 0.70 µM against CBP, EP300, H3K27 and SOX2. DS17701585 can be used for cancer research.

MC2652 (compound 1a) is a potent LSD1 inhibitor. MC2652 displays high inhibiting effects in MV4-11 and NB4 leukaemia cells. MC2652 shows antiproliferative activity against prostate cancer LNCaP cells.

2,4-PDCA (2,4 pyridine dicarboxylic acid) is a broad-spectrum inhibitor of 2OG oxygenase, including JmjC domain-containing family of histone demethylases (JHDMs). 2,4-PDCA is a target chemical in the field of bio-based plastics.

YM458 is a potent EZH2 and BRD4 dual inhibitor with IC50s of 490 nM and 34 nM, respectively. YM458 inhibits cell proliferation and colony formation and induces cell cycle arrest and apoptosis in solid cancer cells. YM458 can be used for researching anticancer.

OXF BD 02 is a selective inhibitor of BRD4(1) (the first bromodomain of BRD4) with IC50 value of 382 nM.

(2S,3R)-LP99 is a potent and selective BRD7 and BRD9 inhibitor with an KD of 99 nM for BRD9. (2S,3R)-LP99 inhibits the association of BRD7 and BRD9 to acetylated histones in vitro and in cells. (2S,3R)-LP99 demonstrates that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion.

ET-JQ1-OH is an allele-specific BET inhibitor.

S1427 is a tranylcypromine-derived LSD1 inhibitor with the IC50 of 390 nM and Ki of 80 nM. S1427 exhibits desirable hERG channel inhibition and microsomal stability profiles. Inhibition of LSD1 partially reduces the proliferation of cancer cells.

FY-56 is a highly potent and selective LSD1/KDM1A inhibitor (IC50=42 nM) and exhibits high selectivity over MAO-A/B. FY-56 induces differentiation of MOLM-13 and MV4-11 cell and has the potential for AML research.

PROTAC_ERRα is a potent and selective ERRα degrader. PROTAC_ERRα induces proteasomal degradation and has capable of specifically degrading ERRα protein by >80%.

Thalidomide-NH-C4-NH-Boc is a novel, potent, and selective class of Bromodomain-containing protein 4 (BRD4) and Bromodomain-containing protein 2 (BRD2) degrader for the development of therapeutics to treat cancers.

EML425 is a potent and selective CREB binding protein (CBP)/p300 inhibitor with IC50s of 2.9 and 1.1 μM, respectively.

(S)-MRTX-1719 (example 16-7) is the S-enantiomer of MRTX-1719. (S)-MRTX-1719 is a PRMT5/MTA complex inhibitor, with an IC50 of 7070 nM.

Tazemetostat (EPZ-6438) hydrochloride is a potent, selective and orally active EZH2 inhibitor with IC50 values of 11 and 16 nM for EZH2 peptide and nucleosome, respectively. Tazemetostat hydrochloride can be used for cancer research.

EZM0414 is a potent, selective, and orally bioavailable inhibitor of Histone-lysine N-methyltransferase SETD2.

TH-6 is a potent HDAC inhibitor with IC50s of 0.115, 0.135, 0.242, 0.138, 2.120 µM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, respectively. TH-6 inhibits cell migration and invasion. TH-6 induces apoptosis and cell cycle arrest at G2/M phase. TH-6 shows anti-tumor activity.

MIND4-19 is a potent SIRT2 inhibitor with an IC50 value of 7.0 μM. MIND4-19 can be used for researching Huntington's disease.

Sirtuin modulator 2 (Compound 132) is a sirtuin modulator with an ED50 equal or less than 50 μM.

QA-68 (QA-68-ZU81) is a potent bromodomain-containing protein 9 (BRD9) degrader. QA-68 can inhibit cell cycle progression and cell colony formation. QA-68 has antiproliferative activity against acute myeloid leukemia (AML) cell lines.

B026 is a selective, potent, orally active p300/CBP histone acetyltransferase (HAT) inhibitor with IC50 values of 1.8 nM and 9.5 nM for p300 and CBP enzyme, respectively. B026 has anticancer activity for androgen receptor-positive (AR+) prostate cancer cell lines.

Purinostat mesylate is a selective inhibitor of HDAC. Purinostat mesylate inhibits class I and class IIb HDACs with IC50s from 0.81 to 11.5 nM. Purinostat mesylate induces apoptosis and affects cell cycle of LAMA84 and 188 BL-2 cells, and shows potently anti-leukemia effects in vivo. Purinostat mesylate can be used for the research of lymphoblastic leukemia.

Bomedemstat (IMG-7289) hydrochloride is an orally active and irreversible lysine-specific demethylase 1 (LSD1) inhibitor. Bomedemstat hydrochloride can increase H3K4 and H3K9 methylation, and then alter gene expression. Bomedemstat hydrochloride shows anti-cancer activities, inhibits cancer cell proliferation and induces apoptosis.

cis-4-Br-2,5-F2-PCPA (S1024) is a selective inhibitor of lysine-specific demethylase 1 (LSD1), with a Ki value of 94 nM instead of 8.4 μM for LSD2. There is aberrant expression of LSD1 in cancer stem cells, cis-4-Br-2,5-F2-PCPA inhibits LSD1 cell proliferation and by increasing the level of dimethylated histone H3 at K4 (H3K4) in CCRF-CEM cells.

GNE-064 (compound 5) is a selective, oral and highly soluble inhibitor of the SMARCA4, SMARCA2 and PBRM1 bromodomains 5. GNE-064 inhibits SMARCA4 with an IC50 of 0.035 μM and inhibits SMARCA2 with an EC50 of 0.10 μM. GNE-064 possess Kds with 0.01, 0.016, 0.018 and 0.049 μM for SMARCA4, SMARCA2, PBRM1 bromodomains 5 and PBRM1 bromodomains 2, repectively. GNE-064 can be used as a chemical probe for the research of drug synthesis.

DY-46-2 is a high potency and selectivity novel non-nucleoside DNA methyltransferase 3A (DNMT3A) inhibitor with an IC50 value of 0.39 μM.

EM127 (compound 11c) is a SMYD3 covalent inhibitor with high selectivity, high affinity (KD=13 μM) and site-specificity. EM127 effectively inhibits ERK1/2 phosphorylation and reduces transcriptional regulation of SMYD3 target genes. EM127 effectively and prolongedly impairs methyltransferase activity. EM127 can be used in cancer research, particularly in SMYD3 positive tumours.

DKFZ-748 is a selective HDAC10 inhibitor (pIC50=7.66), and shows anti-tumor activity.

UNC1021 is a selective L3MBTL3 inhibitor with an IC50 of 0.048 μM.

DDO-2093 dihydrochloride is a potent MLL1-WDR5 protein-protein interaction inhibitor (IC50=8.6 nM; Kd=11.6 nM) with antitumor activity. DDO-2093 dihydrochloride selectively inhibits the catalytic activity of MLL complex.

SAHA-OH is a selective HDAC6 inhibitor (IC50=23 nM), shows a 10- to 47-fold selectivity for HDAC6 compared to HDAC 1, 2, 3, and 8. SAHA-OH shows anti-inflammatory activity, and attenuates macrophage apoptosis.

CRA-026440 hydrochloride is a potent, broad-spectrum HDAC (HDAC) inhibitor. The Ki values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM respectively. CRA-026440 hydrochloride shows antitumor and antiangiogenic activities.

I-BET432 is a BET inhibitor. I-BET432 inhibits BRD4 N-terminal bromodomain (BD1) and the C-terminal bromodomain (BD2) with pIC50 values of 7.5 and 7.2, respectively. I-BET432 can be used as an oral candidate quality molecule for the research of multiple oncology and inflammatory diseases.

MS8815 is a selective enhancer of zeste homolog 2 (EZH2) PROTAC degrader. MS8815 has inhibition activity for EZH2 with an IC50 value of 8.6 nM. MS8815 can be used for the research of triple-negative breast cancer (TNBC).

MM-401 (TFA) is a MLL1 H3K4 methyltransferase inhibitor. MM-401 inhibits MLL1 activity (IC50 = 0.32 µM) by blocking MLL1-WDR5 interaction. MM-401 can induce cell cycle arrest, apoptosis and differentiation. MM-401 can be used for the research of MLL leukemia.

BI-7273 is a potent, selective, and cell-permeable BRD9 BD Inhibitor.

INCB059872 dihydrochloride is a potent, orally active, selective and irreversible Lysine-Specific Demethylase 1 (LSD1) inhibitor. INCB059872 dihydrochloride can be used for the research of myeloid leukemia.

Zavondemstat is an inhibitor of histone lysine demethylase 4D (KDM4D) with antineoplastic activity.

CPI-4203 is a potent KDM5A inhibitor with an IC50 of 250 nM. CPI-4203 is competitive with 2-oxoglutarate (2-OG). CPI-4203 is structurally related to CPI-455 but is less potent.